The causes of disc degeneration are unknown, but understanding its mechanisms is crucial to advancing treatment. The disc is composed of the nucleus pulposus, a hydrated gel, that is contained by the annulus fibrosus, a highly organized fibrocartilage ring. Under normal conditions a hydrostatic pressure is maintained within the nucleus pulposus, generating tensile stresses within the annulus fibrosus. During the early degenerative process the nucleus pulposus becomes less hydrated and more fibrotic, with mechanical consequences of decreased pressure and increased stiffness within the nucleus. This increases the loading and deformation of the annulus. These early nucleus changes are followed by structural and mechanical changes throughout the disc in more advanced disc degeneration. We hypothesize that increased loads and deformations in the annulus fibrosus, which are brought about by decreased pressure and increased stiffness in the nucleus pulposus, together with cyclic fatigue loading, are important mechanisms in disc degeneration. Altered loading of the annulus fibrosus may mediate degeneration through a direct mechanical fatigue mechanism, through biological processes, or a combination of both. Our study is designed to uncouple the roles of mechanical and biological factors, focusing here upon the mechanical factors. We employ a novel model to alter disc loading in a sheep cadaver that combines a chemonucleolytic agent, chondroitinase-ABC (C-ABC), to decrease pressure, with a collagen crosslinking agent, genipin, to increase stiffness. Aim 1 Apply a cadaveric model of degeneration that alters the annulus fibrosus loading. Inject the nucleus pulposus according to four groups: C-ABC (to decrease pressure), genipin (to increase crosslinking), a combination of C-ABC and genipin, and sham control. Measure the mechanical and structural changes to A) the nucleus pulposus, and B) the motion segment. Aim 2 Apply cyclic load to motion segments with modified nucleus pulposus according to the four groups in Aim 1. Measure the mechanical and structural changes to A) the nucleus pulposus and annulus fibrosus, B) the motion segment. Aim 3 Calculate altered stresses and strains in the annulus fibrosus due to nucleus modification using a finite element model with a fiber-induced constitutive description of the annulus.